Stable oral solutions for combined API
The present invention relates to a homogeneous, stable, and palatable pharmaceutical solution comprising baclofen, sorbitol and naltrexone.
1. A pharmaceutical composition comprising, in the form of a solution:
baclofen or a pharmaceutically acceptable salt thereof, sorbitol or a pharmaceutically acceptable salt thereof, and naltrexone or a pharmaceutically acceptable salt thereof as active ingredients,
an acetate or citrate buffer, and
optionally, at least one preservative, flavoring agent, or a combination thereof;
wherein the solution has a pH of between 4 and 7.
2. The composition of claim 1 , wherein sorbitol or a pharmaceutically acceptable salt thereof and naltrexone or a pharmaceutically acceptable salt thereof are present in a relative weight ratio (sorbitol or a pharmaceutically acceptable salt thereof/naltrexone or a pharmaceutically acceptable salt thereof) between 100/1 and 500/1.
3. The composition of claim 1 , wherein baclofen or a pharmaceutically acceptable salt thereof and naltrexone or a pharmaceutically acceptable salt thereof are present in a relative weight ratio (baclofen or a pharmaceutically acceptable salt thereof/naltrexone or a pharmaceutically acceptable salt thereof) between 2/1 and 20/1.
4. The composition of claim 1 , wherein baclofen or a pharmaceutically acceptable salt thereof, sorbitol or a pharmaceutically acceptable salt thereof and naltrexone or a pharmaceutically acceptable salt thereof are present in the relative weight ratio of about 8.6/300/1.
5. The composition of claim 1 , wherein the pH of the solution is about 5.5.
6. The composition of claim 1 , wherein the at least one flavoring agent is isoamyl acetate or vanillin.
7. The composition of claim 1 , wherein the at least one preservative is a paraben.
8. The composition of claim 7 , wherein the at least one preservative is methyl paraben, propyl paraben, or a combination thereof.
9. The composition of claim 8 , wherein the methyl paraben, propyl paraben, or a combination thereof is present in a concentration of about 0.18% w/v and about 0.02% w/v, respectively.
10. The composition of claim 1 , comprising:
baclofen or a pharmaceutically acceptable salt thereof, sorbitol or a pharmaceutically acceptable salt thereof, and naltrexone or a pharmaceutically acceptable salt thereof as active ingredients in a relative weight ratio of about 8.6/300/1,
an acetate buffer,
about 0.18% w/v of methyl parahydroxybenzoate and 0.02% w/v propyl parahydroxybenzoate, and
about 0.04% w/v of isoamyl acetate;
wherein the solution has a pH of about 5.5.
11. The composition of claim 1 , which is free of paraben and wherein the buffer is an acetate buffer.
12. The composition of claim 1 , comprising at least one further compound selected from the group consisting of antioxidants, emulsifiers, viscosity modifiers, sweeteners, flavor enhancers, coloring agents, co-solvents, solubilizers, and combinations thereof.
13. A method of treating Charcot-Marie-Tooth disease, comprising administering the composition of claim 1 to a subject in need thereof.
14. A container comprising the composition of claim 1 .
15. A kit comprising the container of claim 14 and instructions.
16. A method for preparing the composition of claim 1 , comprising the steps of: providing baclofen or a pharmaceutically acceptable salt thereof, sorbitol or a pharmaceutically acceptable salt thereof, and naltrexone or a pharmaceutically acceptable salt thereof; and admixing said baclofen or a pharmaceutically acceptable salt thereof, sorbitol or a pharmaceutically acceptable salt thereof, and naltrexone or a pharmaceutically acceptable salt thereof in a citrate or acetate buffer to form a solution with a pH between 4 and 7.
17. The composition according to claim 1 , wherein the pH of the solution buffer is between 4.5 and 5.5.
18. The composition of claim 1 , wherein sorbitol or a pharmaceutically acceptable salt thereof and naltrexone or a pharmaceutically acceptable salt thereof are present in a relative weight ratio (sorbitol or a pharmaceutically acceptable salt thereof/naltrexone or a pharmaceutically acceptable salt thereof) between 200/1 and 400/1.
19. The composition of claim 1 , wherein baclofen or a pharmaceutically acceptable salt thereof and naltrexone or a pharmaceutically acceptable salt thereof are present in a relative weight ratio (baclofen or a pharmaceutically acceptable salt thereof/naltrexone or a pharmaceutically acceptable salt thereof) between 5/1 and 10/1.
20. The composition of claim 1 , wherein said baclofen or a pharmaceutically acceptable salt thereof is (RS) baclofen, said sorbitol or a pharmaceutically acceptable salt thereof is D-sorbitol, and said naltrexone or a pharmaceutically acceptable salt thereof is naltrexone HCl.